title: Ten-month laryngeal allograft survival with use of pulsed everolimus and anti-alphabeta T-cell receptor antibody immunosuppression.
abstract: OBJECTIVE
  The risks of daily immunosuppression limit the use of laryngeal transplantation as a reconstructive option. Pulsed immunosuppressive dosing can lessen these risks. The study objective was to develop a long-term pulsing regimen that minimizes exposure to immunosuppressive agents.
  
  
  METHODS
  Rat laryngeal transplantation was performed. Everolimus (1 mg/kg per day) and anti-c41 T-cell receptor (TCR) antibodies (250 microg) were given for 7 days beginning 1 day before transplantation and for 5 days beginning on day 90 after transplantation. On day 180, group 1 (n = 5) received the initial regimen for 3 days, and group 2 (n = 5) received everolimus (1 mg/kg per day) until euthanization, which occurred when parathyroid hormone (PTH) levels dropped to less than 11 pg/mL or at 300 days.
  
  
  RESULTS
  Four of the 5 rats in group 1 had normal PTH levels at 300 days. The PTH level for 1 rat was less than 11 pg/ mL at 270 days. In group 2, none of the 5 rats had normal PTH levels at 300 days. Two had PTH levels below 11 pg/mL at 270 days, and 3 had PTH levels below 11 pg/mL at 300 days. The allografts that survived beyond 300 days had an essentially normal histologic appearance.
  
  
  CONCLUSIONS
  Pulsed immunosuppression prevented allograft rejection for 10 months and was more effective than daily everolimus. Short-term perioperative therapy followed by pulsed, tapered dosing is a viable alternative to traditional regimens and may decrease associated risks.
authors.affiliation: Cleveland Clinic Head and Neck Institute, Cleveland, Ohio, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Lott
authors.forename: Jonathon O
authors.initials: JO
authors.lastname: Russell
authors.forename: Samir S
authors.initials: SS
authors.lastname: Khariwala
authors.forename: Olivia
authors.initials: O
authors.lastname: Dan
authors.forename: Marshall
authors.initials: M
authors.lastname: Strome
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D000068338:Everolimus; D006085:Graft Survival; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007830:Larynx / Q000637:transplantation*; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood; D020551:Pulse Therapy, Drug; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014184:Transplantation, Homologous
chemical_list: D000906:Antibodies; D007166:Immunosuppressive Agents; D010281:Parathyroid Hormone; D016693:Receptors, Antigen, T-Cell, alpha-beta; D000068338:Everolimus; D020123:Sirolimus